Role of the p38 MAPK signaling pathway in mediating interleukin-28A-induced migration of UMUC-3 cells

Lee,Se-Jung; Kim,Wun-Jae; Moon,Sung-Kwon

doi:10.3892/ijmm.2012.1064

Role of the p38 MAPK signaling pathway in mediating interleukin-28A-induced migration of UMUC-3 cells

Authors:
- Se-Jung Lee
- Wun-Jae Kim
- Sung-Kwon Moon
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Affiliations: Department of Biotechnology, Chungju National University, Chungju, Chungbuk 380-702, Republic of Korea, Personalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea
Published online on: July 16, 2012 https://doi.org/10.3892/ijmm.2012.1064
Pages: 945-952

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Abstract

Although interleukin-28A (IL-28A) is believed to have an antiviral effect, its role in tumor migration requires further examination. The present study was intended to verify the effect of IL-28A on the migration of UMUC-3 bladder cancer cells. IL-28A and its receptor IL-28AR1 mRNA were detected in UMUC-3 cells. Although exogenous IL-28A showed no effect on cell proliferation, a wound-healing migration assay showed that the migration of UMUC-3 cells was induced by IL-28A. Furthermore, treatment of the cells with IL-28A significantly promoted MMP-9 expression via binding activities of NF-κB and AP-1. IL-28A also induced the activation of p38 MAPK and Jak2-Stat2 signaling. Using the p38 MAPK inhibitor SB203580 and the dominant-negative plasmid DN-p38, we found evidence that the inhibition of p38 MAPK signaling suppressed the effects of IL-28A including wound-healing migration and MMP-9 expression by activation of NF-κB and AP-1 binding in UMUC-3 cells. However, Jak-2 inhibition by AG490 did not affect IL-28A-induced migration of UMUC-3 cells. Collectively, we suggest for the first time that the p38 MAPK pathway mediates IL-28A-induced cell migration through MMP-9 expression by activating NF-κB and AP-1 binding motifs.

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